Cell division is the fundamental process by which living organisms grow and reproduce. The cycle of cell division consists of three principle events: interphase, mitosis, and cytokinesis. During interphase, replication of the DNA and production of essential proteins are synthesized. In mitosis, the nuclear material is divided and separated to opposite halves of the cell. In cytokinesis, the cell cytoplasm is divided. These cell cycle events are regulated by various cell division regulators.
A group of cell division regulatory proteins active in the interphase is related to nuclear redistribution and modulation. These regulatory proteins include the proliferating cell nuclear antigen (PCNA) which is identified as the DNA polymerase-.delta. auxiliary protein (Prelich, G. et al. (1987) Nature 326: 517-520), the Schizosaccharomyces pombe Cdc21p gene (Coxon, A. et al. (1992) Nucleic Acids Res. 20: 5571-5577), and a murine cell cycle-specifically modulated nuclear protein, p38-2G4 (Radomski, N. and Jost, E. (1995) Exp. Cell Res. 220: 434-445). p38-2G4 is a nuclear protein of 38 kDa and is a murine homolog of S. pombe Cdc21p gene product. p38-2G4 shows its highest expression between the G1 phase and the mid S phase and contains a number of putative phosphorylation sites, a cryptic nuclear localization signal, and an amphipathic helical domain.
The process of cytokinesis and septum formation has been well studied. Cytokinesis is believed to be mediated by the filaments and other components formed from GTP-binding proteins (Mori, et al. (1996) Cytogenet. Cell Genet. 73: 224-227). Septins are a family of proteins that are involved in septum formation. (Longtine, M. S. et al. (1996) Curr. Opin. Cell Biol. 8:106-119). In yeast, four gene products (CDC3, CDC10, CDC11, and CDC12) are members of this family and are associated with the "bud filament" which is located directly inside the cytoplasmic membrane. Mutations in any of the CDC genes disrupts cytokinesis and gives rise to multi-nucleated cells with abnormal bud growth.
Homologs of the yeast septins have been found in Drosophila melanogaster (Sep2), mouse (H5; proliferation associated protein 1; Nakagawa, Y. et al. (1996) unpublished), and human (KIAA0128; cell division control related protein; Zieger, B. et al. (1997) J. Clin. Invest. 99: 520-525; Nagase, T. et al. (1996) DNA Res. 3: 321-329). Most of these proteins share three domains rich in basic amino acids that are a common motif of GTP-binding proteins and of the GTPase superfamily. The first of these three domains, the sequence GXXGXGKST, is thought to be an ATP/GTP-binding site (P-loop) that may be involved in septin assembly or function (Saraste, M. et al. (1990) Trends Biochem. Sci. 15:430-34). Most of the known septins also contain predicted coiled-coil domains of 35 to 98 amino acids near the C-termini (Longtine et al., supra). These domains may be involved in homotypic or heterotypic interactions among the septins themselves and/or with other proteins.
The discovery of three new human cell division regulators and the polynucleotides encoding them satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention, and treatment of inflammation and disorders associated with cell proliferation and apoptosis.